This proposal seeks to answer the question: Will maintenance of normal or virtually normal blood glucose prevent, decrease, or reverse the microvascular (and possibly macrovascular) complications of insulin dependent diabetics. Suitable patients will be randomized into a conventionally treated control group and an experimental group treated with 4 insulin injections per day (or by continuous subcutaneous infusion). During a feasibility trial period of 1-2 years and a definitive period of 7 years, diabetics will be monitored by fundus photographs, fluorescein angiograms, renal function tests, nerve conduction tests, cardiophysiological tests, and muscle capillary basement membrane thickness. Home blood glucose monitoring will be used to facilitate and verify the "tight" regulation of the experimental group. Statistical analysis of the data from all participating centers should give a broadly applicable answer to this critical question in diabetes management.